Ketones tritiation

Since ivermectin (= 22,23-dihydroavermectin B ) is obtained by catalytic reduction of avermectin B, the same procedure using tritium gas convenientiy affords tritiated ivermectin (22,23- [JT]-22,23-dihydroavermectin B ). The preparation of a tritiated derivative containing a 22,23-double bond starts with the readily available 5-ketone, which is reduced with [JT]-sodium borohydride stereospecificaHy to a 5- [JT]-derivative (40). Carbon-14 labeled avermectins can be obtained by a biosynthetic process using sodium (l- C)propionate as labeled precursor (48). 

The naturally occurring copabomeol (474) was oxidized to ketone 475 and then labelled with tritium at the bridgehead by heating with strong base and tritiated alcohol at high temperatures (Scheme 61) (231a). Reduction with sodium in ethanol yielded labelled copabomeol (474 ), which was administered to C.japonica (231b). 

P,P-Bis(alkylthio)-a,P-unsaturated ketones are selectively reduced in a 1,2-manner to the corresponding allylic alcohols by tritiated NaBH4 in ethanol. ° Enaminones are similarly reduced by tritiated... 

Such chains might have a small probability of propagating by dissociation of the complex, but could also lead to the cyclic ketone above in a true termination reaction, or in the reaction with tritiated acetic acid. In the... 

C,3R,5- H2]mevalonic acid is [3Hi while lophenol is [ Hn, " 5]. It must be concluded that, contrary to earlier reports, the 4a-methyl group is lost first. This result is further substantiated by the incorporation of 4a-hydroxy-methyl-4j3-methylcholestan-3j8-ol but not the 4jff-hydroxymethyl isomer. Furthermore, 4j9-methylcholestan-3)S-ol is largely inert. The sequence of events would seem to be that the 4a-methyl is oxidised to a carboxyl group and the 3)3-hydroxyl to a 3-ketone. Decarboxylation of the jS-keto acid is followed by rapid reduction of the 3-ketone back to a 3/9-alcohol. In the presence of tritiated water C-3 and C-4 become radioactive. ... 

Isotopic substitution of hydrogen adjacent to carbonyl occurs when the ketone is passed through a column of alumina loaded with tritiated water (HTO), ° or in gas-chromatography over a stationary phase comprising poly(ethylene glycol) saturated with... 

Conformational analysis " of 3j8-ethoxycarbonyl-3o -phenyltropane, an analogue of pethidine, by n.m.r. spectroscopy, indicated axial preference of the 3a-phenyl group, hence a chair conformation for the piperidine ring (22). However, the intermediates 3a-diphenylhydroxymethyl-3/3-tropanol (23) and 3a-phenyl-3)8-tropanylphenyl ketone (24) favour the boat form. Pyrolysis of (22) led, with the boat form in the transition state, to 7-aza-3-chloro-7-methyl-l-phenyl-8-oxobicyclo[4,2,l]nonane (25), based on elemental analysis and mass spectrum. ( —)-1-p-Butoxyphenyl [a- H]hyoscyaminium bromide was prepared from ( —)-hyoscyamine and p-butoxy[a- H]benzyl bromide. N-Methyl [l- H]- psicaine neu and U-tritiated psicaine have also been described." ... 

Aldehydes and ketones are unaffected by sodium cyanoborohydride in neutral solution, but they are readily reduced to the corresponding alcohol at pH = 3-4 by way of the protonated carbonyl group. By previous exchange of the hydrogens of the borohydride for deuterium or tritium, by reaction with D2O or tritiated water, an efficient and economical route is available for deuteride or tritiide reduction of aldehydes and ketones. 

Pulse radiolysis of penicillamine in aqueous solution gives thiyl radicals RS% Amax 330 nm, and the radical anion RSSR-, Amax 450 nm, formed from RS and RS / Photolysis of propanethiol tritiated at SH, in the presence of a hydrogen donor, results in tritium scrambling in the propyl group and in the hydro n donor, suggesting that such a system is a useful source of H atoms in solution. In eased yields of the products of sensitized photodecarboxylation of R X CHj COaH (X = O, S, or NH) are obtained in the presence of thiophenol as hydrogen donor. Butane-thiol quenches triplet acetophenone only slowly (At = 1.4 x 10 1 mol s ), and it can be included in the reaction systems of ketone photo-reactions as a radical trap without interfering with the photo-excited substrate. ... 

Cyclohepta-amylose has been converted into the phosphates (21)—(23), which were examined as catalysts for the hydrolysis of 4-nitrophenyl tetrahydropyranyl ether at low pH and for the exchange of 4-t-butylphenacyl alcohol (tritiated in the a-methylene group) at high pH. All three isomers, as the phosphate dianions, were effective catalysts for the latter reaction in which the functional group assists enolization of the bound ketone. Only the 3-phosphate (22) showed net catalysis of the hydrolysis of the ether, which was bound and hydrolysed with the assistance of a monoanionic phosphoric acid group. 

Finally, the use of isotopes in carbon-acid substrates is an invaluable tool for the determination of the stereochemistry of the enzymatic proton transfer. In contrast to organic reactions, stereospecific proton transfers are the rule, rather than the exception, in enzymatic reactions, owing to the inherently asymmetric nature of the protein surface. An example is the pair of isotopic exchange reactions between dihydroxyacetone phosphate and tritiated water catalysed by the enzymes aldolase and triose phosphate isomerase [17]. In the two cases a different a-hydrogen of the ketone is exchanged with water, leading to the two discrete monotritiated derivatives 1 (labelled by the isomerase) and 2 (labelled by the aldolase) ... 

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